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J. Biol. Chem., Vol. 275, Issue 24, 17925-17928, June 16, 2000
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,
,
From the Institute of Molecular and Cell Biology, 30 Medical Dr.,
Singapore 117609, Republic of Singapore
Sex-specific elimination of cells by apoptosis
plays a role in sex determination in Caenorhabditis
elegans. Recently, a mammalian pro-apoptotic protein named F1A
has been identified. F1A
shares extensive homology throughout the
entire protein with the C. elegans protein, FEM-1, which is
essential for achieving all aspects of the male phenotype in the
nematode. In this report, the role of FEM-1 in apoptosis was
investigated. Overexpression of FEM-1 induces caspase-dependent apoptosis in mammalian cells. FEM-1
is cleaved in vitro by the C. elegans caspase,
CED-3, generating an N-terminal cleavage product that corresponds to
the minimal effector domain for apoptosis. Furthermore, CED-4
associates with FEM-1 in vitro and in vivo in
mammalian cells and potentiates FEM-1-mediated apoptosis. Similarly,
Apaf-1, the mammalian homologue of CED-4 was found to associate with
F1A
. These data suggest that FEM-1 and F1A
may mediate apoptosis
by communicating directly with the core machinery of apoptosis.
These authors contributed equally to this work.
§
To whom correspondence should be addressed. Tel.: 65-8743740; Fax:
65-7791117; E-mail: mcbyuck@imcb.nus.edu.sg.
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